Changes in Inflammatory Cytokines Are Related to Impaired Glucose Tolerance in Offspring of Type 2 Diabetic Subjects

Abstract

OBJECTIVE—We sought to determine whether levels of inflammatory markers and different cytokines are abnormal in nondiabetic offspring of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—Cytokine levels were measured in 19 healthy control subjects and 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance [NGT] and 20 with impaired glucose tolerance [IGT]). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. RESULTS—Levels of C-reactive protein and inflammatory cytokines were elevated in nondiabetic offspring of type 2 diabetic subjects. Interleukin (IL)-1β was increased in the NGT group and decreased in the IGT group. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) were increased in both groups. IL-1β and -Ra levels correlated inversely (P < 0.05) with rates of whole-body glucose uptake and IL-1β positively with visceral fat mass (P < 0.05) in normoglycemic offspring. CONCLUSIONS—Nondiabetic offspring of type 2 diabetic subjects have changes in the levels of inflammatory cytokines. The level of IL-1Ra seems to be the most sensitive marker of cytokine response in the pre-diabetic state.